β-淀粉样蛋白诱导的大鼠神经元损伤及神经生长因子的影响  

NEURONAL DAMAGE INDUCED BY *-AMYLOID IN NEONATAL RAT CORTICAL NEURONS AND EFFECTS OF NERVE GROWTH FACTOR

作　　者：谈冶雄[1] 陶学斌[1] 袁默[2] 李万亥[1] 

机构地区：[1]第二军医大学药学院中西药药理研究室,上海200433 [2]中国人民解放军第二炮兵262医院,北京100088

出　　处：《解放军药学学报》1998年第1期4-8,共5页Pharmaceutical Journal of Chinese People's Liberation Army

摘　　要：实验测定β-淀粉样蛋白(β-AP)刺激新生大鼠培养神经元上清液中,LDH活性及神经元MTT值,初步研究了β-AP诱导的神经元毒性。结果发现,β-AP诱导的神经元培养上清液LDH活性增高与剂量呈正相关,并呈时间依赖性,说明β-AP具有特异的神经元毒性。实验过程中,对培养神经元结构的形态学观察也与测定结果符合。提示,β-AP在早老性痴呆的发生发展过程中具有重要作用。NGF对β-AP诱导神经元损伤的作用与剂量密切相关,在较低浓度(50～200U·ml^(-1))下,可有效地抑制LDH的活性增高和MTT值降低,具有保护作用;在较高浓度下(>200U·ml^(-1)),却出现与β-AP协同的神经毒性,加重损伤程度。The damage effects of β-AP (β-amyloid protein), induced eytotoxicity in cultured neona-tal rat cortical neurons were studied. Intracellular LDH release, 3- (4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cellular morphological changes were used to evaluate the ef-fect of β-amyloid. In this study, (3-amyloid (1, 2, 5, 10mg·?ml) dose-dependently and time-dependently promoted LDH release in cultured neonatal rat cortical neurons, and cellular morphological changes be-came more obvious with the concentration of β-amyloid in creasing. All of these suggest that β-amyloid could induce neurotoxicity in cultured rat cortical neurons. Nerve Growth Factor (50-200 U·ml-1)was shown dose - dependently to inhibit LDH release and increase MTT value which induced by β-amyloid (2mg·ml-1). It means that NGF protect cultured neurons against the damage induced by β-amyloid and the morphology improved. But high concentration of NGF (≥ 500 U ·ml-1) increased neurotoxicity in-duced by β-amyloid.

关 键 词：早老性痴呆 Β-淀粉样蛋白 神经元 损伤 神经生长因子 

分 类 号：R965[医药卫生—药理学]